1. Field of Invention
The invention relates to a process for selectively modifying pendent functionalities of polymers having hydrolytically unstable backbone functionalities and to products produced thereby.
2. Description of Related Art
It is frequently desirable to modify the properties of a polymer by modifying the pendent functionalities of the polymer. Such is the case for polymers having pendent protective groups remaining from polymerization. These relatively inert pendent groups can be necessary for polymerization, but undesirable in the product polymer itself.
For example, U.S. Pat. No. 6,120,491 reports that certain polycarbonates, polyarylates and poly(alkylene oxide) polymers based on amino acids, such as those disclosed in U.S. Pat. Nos. 5,099,060, 5,198,507, 5,216,115 and 5,658,995, cannot be prepared by conventional solution processes from monomers having free carboxylic acid groups. Removable protecting groups must be incorporated into the polymer that can be cleaved after the polymer is formed, without significant degradation of the polymer backbone. The protecting groups are needed to prevent cross-reaction of these otherwise free carboxylic acid groups with (i) phosgene, phosgene equivalents or diacid chlorides used in the preparation of polycarbonates and ester carbonate copolymers, and (ii) carbodiimide reagents used in the preparation of polyarylates.
The polymers with protected carboxylic acid groups are limited in specific bioresorption applications because of their slow rate of degradation and significant hydrophobicity. The free acid form of the polymers, in which the ester protecting groups have been removed from the pendent carboxylic acid chains of the diphenol based component, would be less hydrophobic and thus would be expected to exhibit somewhat increased degradation rates desirable in bioresorbable polymers.
In polycarbonates, polyarylates and poly(alkylene oxide) block copolymers thereof prepared from tyrosine-derived diphenol monomers, the backbone contains bonds that are designed to degrade in aqueous media (acidic, neutral, or basic). Thus, the selective removal of any carboxylic acid protecting groups is a challenge. According to the '491 patent, the ester protecting groups of such polymers cannot be removed by conventional hydrolysis techniques without unacceptable degradation of the polymer backbone.
The '491 patent purports to solve this problem in providing a process comprising controlling monomer feed ratios of desaminotyrosyl tyrosine ethyl ester (DTE) and desaminotyrosyl tyrosine benzyl ester (DTBn) monomers, followed by polymerization using phosgene or a phosgene equivalent. The desired copolymer is isolated, and subsequently subjected to hydrogenolysis to effect benzyl ester removal, yielding the free carboxylic acid copolymer for all compositions (e.g., the entire copolymer compositional range of the poly(DTE-co-X % DT) carbonates) (where DT is desaminotyrosyl tyrosine free acid) with controlled molecular weights. Although this synthetic strategy enables the preparation of the desired composition of matter, the economics of the process (viz., support of additional monomer manufacture, additional isolation/handling protocols, removal of catalyst residues, capital expenditure on pressure hydrogenation equipment, and increased waste streams) would jeopardize wide-use commercial acceptance.
Accordingly, it is desired to provide an alternative solution to the problem of selective modification of pendent groups in polymers with an acceptable low level of hydrolytically unstable backbone cleavage.
All references cited herein are incorporated herein by reference in their entireties.